Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.4.1.1 (pyruvate carboxylase)
1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rather complete model of the gluconeogenic pathway was used, with the known separate pools of mitochondrial and cytosolic oxalacetate, malate and aspartate. The fumarase, malate dehydrogenase and glutamate oxalacetate transaminase reactions were assumed to be isotopically actively reversible, but none at isotopic equilibrium. Malate was assumed to exchange actively between the mitochondria and cytosol, while aspartate exchange was more limited, in agreement with the known electrogenic nature of aspartate export from the mitochondria. This model was fit to 14C data obtained in hepatocyte studies, and to the whole rat 14C data obtained by Heath and Rose (Biochem J. 227, 851-876, 1985). The latter data were easily fit to our model, when a single mitochondrial oxalacetate pool was assumed. However, invoking two mitochondrial oxalacetate pools, as proposed by Heath and Rose, with the oxalacetate formed via pyruvate carboxylase preferentially channelled to gluconeogenesis, could not be fit with the known differences in scrambling in glucose and glutamate produced from L[3-14C]lactate.
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PMID:Dicarboxylic acid fluxes during gluconeogenesis. No channelling of mitochondrial oxalacetate. 774 40

Although pyruvate carboxylase associated with both mitochondrial aspartate aminotransferase and malate dehydrogenase, it had a higher affinity for the amino-transferase. Furthermore, the aminotransferase enhanced dissociation of malate dehydrogenase from pyruvate carboxylase. Glutamate dehydrogenase did not associate with pyruvate carboxylase alone, but it apparently associated with the pyruvate carboxylase-aminotransferase complex, and malate dehydrogenase associated with the resulting ternary complex. Citrate synthase and other proteins tested did not associate with pyruvate carboxylase. However, citrate synthase associated with the pyruvate carboxylase-malate dehydrogenase complex. Apparently as a consequence of these heteroenzyme interactions, the rate of the pyruvate carboxylase reaction was slightly greater when coupled with malate dehydrogenase or both malate dehydrogenase and citrate synthase than when coupled with citrate synthase alone. In addition, in the presence of both coupling enzymes, the rate of conversion of pyruvate to citrate was higher than predicted on the basis of the Michaelis-Menten relationship of the two coupling enzymes. Therefore, binding of malate dehydrogenase to pyruvate carboxylase enhances pyruvate carboxylase activity. Association of citrate synthase with the malate dehydrogenase-pyruvate carboxylase binary complex does not alter activation of pyruvate carboxylase but results in citrate synthase being more reactive than free citrate synthase with oxalacetate.
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PMID:Interactions between pyruvate carboxylase and other mitochondrial enzymes. 834 77

The purpose of the present investigation was to examine changes in six potential regulators of hepatic gluconeogenesis with normal aging and endurance training: fructose 2,6-bisphosphate (F 2,6-P2), mitochondrial and cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity, PEPCK mRNA, and pyruvate carboxylase and malate dehydrogenase activity. Young (4 months), middle-aged (12 months), and old (22 months) male-Fischer 344 rats (N = 66) were divided into trained and sedentary groups. Trained animals were run 1 h/d, 5 d/wk for 10 weeks at treadmill speeds of 75% age-specific maximal running capacity. Animals were killed at rest, and the right main lobe of the liver was removed. F 2,6-P2 levels were significantly greater in old compared with young animals regardless of training condition (119% and 80% increase in old trained and untrained animals, respectively). No changes were found with training. Rates of cytosolic PEPCK activity declined significantly with age in both trained (1.3 +/- 0.1, 1.0 +/- 0.1, and 0.7 +/- 0.1 mumol/g/min in young, middle-aged, and old, respectively) and untrained (1.3 +/- 0.1, 1.1 +/- 0.1, and 0.8 +/- 0.2 mumol/g/min) groups. Training did not result in any significant differences between age groups. PEPCK gene expression (mRNA) determined by Northern blot analysis decreased 30% in trained and untrained old animals compared to the young counterparts; again, training had no effect in any age group. No significant differences were found in pyruvate carboxylase, mitochondrial PEPCK, or malate dehydrogenase activity with either age or training. These results suggest that previous age-related declines found in hepatic gluconeogenic capacity can be attributed, in part, to changes in F 2,6-P2, cytosolic PEPCK activity, and PEPCK mRNA, but not to alterations in the activities of mitochondrial PEPCK, malate dehydrogenase, or pyruvate carboxylase. Since training had no effect on any regulator studied, the factors responsible for attenuation in the age-related decline in gluconeogenesis with training remain to be determined.
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PMID:Alterations in key gluconeogenic regulators with age and endurance training. 910 46

Saccharomyces cerevisiae accumulates L-malic acid through a cytosolic pathway starting from pyruvic acid and involving the enzymes pyruvate carboxylase and malate dehydrogenase. In the present study, the role of malate dehydrogenase in the cytosolic pathway was studied. Overexpression of cytosolic malate dehydrogenase (MDH2) under either the strong inducible GAL10 or the constitutive PGK promoter causes a 6- to 16-fold increase in cytosolic MDH activity in growth and production media and up to 3.7-fold increase in L-malic acid accumulation in the production medium. The high apparent Km of MDH2 for L-malic acid (11.8 mM) indicates a low affinity of the enzyme for this acid, which is consistent with the cytosolic function in the enzyme and differs from the previously published Km of the mitochondrial enzyme (MDH1, 0.28 mM). Under conditions of MDH2 overexpression, pyruvate carboxylase appears to be a limiting factor, thus providing a system for further metabolic engineering of L-malic acid production. The overexpression of MDH2 activity also causes an evaluation in the accumulation of fumaric acid and citric acid. Accumulation of fumaric acid is presumably caused by high intracellular L-malic acid concentrations and the activity of the cytosolic fumarase. The accumulation of citric acid may suggest the intriguing possibility that cytosolic L-malic acid is a direct precursor of citric acid in yeast.
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PMID:Overexpression of cytosolic malate dehydrogenase (MDH2) causes overproduction of specific organic acids in Saccharomyces cerevisiae. 929 84

Enterocytes from fasted rabbits make glucose from exogenous fructose and dihydroxyacetone at rates of 180 and 91 nmol/min/10(8) cells but do not make glucose from glycerol, aspartate, malate, lactate, alpha-ketoglutarate, glutamate or glutamine. Total activities of phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase and glucose 6-phosphatase in isolated enterocytes are 0.44, 0.60 and 1.90 mumol/min/10(8) cells, and > or = 95% of carboxykinase activity is intramitochondrial. Enterocytes contain marginal glycerol kinase (0.05 mumol/ min/10(8) cells) and essentially no pyruvate carboxylase activities. Enterocyte mitochondria synthesize citrate from exogenous phosphoenolpyruvate and acetylcarnitine at a rate of 2.40 nmol/min/mg protein. Citrate formation is highly dependent on exogenous HCO3 and inhibited strongly by 3-mercaptopicolinate and 1,2,3-benzenetricarboxylate. Citrate synthesis is stimulated consistently by GDP and significantly so by GTP. Citrate production is unaffected by ADP or ATP. Enterocytes from fasted-refed rabbits contain activities of 0.05, 0.12, 0.39 and 0.56 mumol/min/mg cytosolic protein of ATP:citrate lyase, NADP:malate dehydrogenase, glucose 6-phosphate dehydrogenase and NADP:isocitrate dehydrogenase. Activities of NADP:malate dehydrogenase, glucose 6-phosphate dehydrogenase and NADP:isocitrate dehydrogenase are significantly higher in enterocytes from fasted-refed rabbits than those from fasted rabbits. Mitochondrial phosphoenolpyruvate carboxykinase in enterocytes in vivo could convert glycolysis-derived phosphoenolpyruvate to oxaloacetate that, with acetyl CoA, could form citrate for export to support cytosolic lipogenesis as an activator of acetyl CoA carboxylase, a source of carbon via ATP:citrate lyase and of NADPH via NADP:malate dehydrogenase or NADP:isocitrate dehydrogenase.
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PMID:Synthesis of citrate from phosphoenolpyruvate and acetylcarnitine by mitochondria from rabbit enterocytes: implications for lipogenesis. 946 72

The effects of iron deficiency and iron resupply on the metabolism of leaf organic acids have been investigated in hydroponically grown sugar beet. Organic acid concentrations and activities in leaf extracts of several enzymes related to organic acid metabolism were measured. Enzymes assayed included phosphoenol pyruvate carboxylase (PEPC; EC 4.1.1.31), different Krebs cycle enzymes: malate dehydrogenase (MDH; EC 1.1.1.37), aconitase (EC 4.2.1.3), fumarase (EC 4.2.1.2), citrate synthase (CS; EC 4.1.3.7) and isocitrate dehydrogenase (ICDH; EC 1.1.1.42), glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49) and two enzymes related to anaerobic metabolism (lactate dehydrogenase [LDH]; EC 1.1.1.27, and pyruvate decarboxylase [PDC]; EC 4.1.1.1). Iron concentration in leaves was severely decreased by iron deficiency. Iron resupply caused an increase in iron concentrations, reaching levels similar to the controls in 96 h. Iron deficiency induced a 2.3-fold (from 16 to 37 mmol m-2) increase in leaf total organic acid concentration. Organic anion concentrations were still 4-fold higher than the controls 24 h after resupply and decreased to values similar to those found in the controls after 96 h. All measured enzymes had increased activities in extracts of iron-deficient leaves when compared to the controls and generally decreased to control values 24 h after iron addition. These data provide evidence that organic acid accumulation in iron-deficient leaves is likely not due to an enhancement in leaf carbon fixation. Instead, this accumulation could be associated with organic acid export from the roots to the leaves via xylem.
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PMID:Changes induced by Fe deficiency and Fe resupply in the organic acid metabolism of sugar beet (Beta vulgaris) leaves. 1131 12

Enzymatic activities of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) (EC 4.1.1.39), phospho(enol)pyruvate carboxylase (EC 4.1.1.31), NAD malate dehydrogenase (EC 1.1.1.37), and NADP glyceraldehydephosphate dehydrogenase complex including phosphoglycerate kinase (EC 2.7.2.3) and glyceraldehydephosphate dehydrogenase (EC 1.2.1.13) were comparatively assayed in wheat seedlings of the cultivar Lyutestsens 758 grown under normal conditions, water deficiency conditions, and subsequent rehydration. Water stress was found to decrease the activity of all enzymes tested, the effect being most pronounced in case of Rubisco. The content of Rubisco in wheat plants exposed to water deficiency was reduced less significantly than the activity of the enzyme. Preliminary treatment of plant seeds with kartolin-4 (o-isopropyl-N-2-hydroxyethyl carbamate), a preparation with cytokinin activity, reduced the dehydration-induced inhibition of enzymatic activity. Upon a subsequent rehydration, kartolin-4 facilitated rapid recovery of the photosynthetic activity, the process being based on the kartolin-induced stimulation of reparation reactions. Under conditions of water stress, a partial decrease in the activity of carbon metabolism enzymes in vitro was accompanied by complete inhibition of photosynthesis in vivo, perhaps, as a result of an abrupt increase in the stomatal resistance.
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PMID:[Activity of carbon metabolism enzymes in wheat plants treated with kartolin-4 and exposed to water stress]. 1177 26

The beta-cell biochemical mechanisms that account for the compensatory hyperfunction with insulin resistance (so-called beta-cell adaptation) are unknown. We investigated glucose metabolism in isolated islets from 10-12-week-old Zucker fatty (ZF) and Zucker lean (ZL) rats (results expressed per mg/islet of protein). ZF rats were obese, hyperlipidemic, and normoglycemic. They had a 3.8-fold increased beta-cell mass along with 3-10-fold increases in insulin secretion to various stimuli during pancreas perfusion despite insulin content per milligram of beta-cells being only one-third that of ZL rats. Islet glucose metabolism (utilization and oxidation) was 1.5-2-fold increased in the ZF islets despite pyruvate dehydrogenase activity being 30% lowered compared with the ZL islets. The reason was increased flux through pyruvate carboxylase (PC) and the malate-pyruvate and citrate-pyruvate shuttles based on the following observations (% ZL islets): increased V(max) of PC (160%), malate dehydrogenase (170%), and malic enzyme (275%); elevated concentrations of oxaloacetate (150%), malate (250%), citrate (140%), and pyruvate (250%); and 2-fold increased release of malate from isolated mitochondria. Inhibition of PC by 5 mm phenylacetic acid markedly lowered glucose-induced insulin secretion in ZF and ZL islets. Thus, our results suggest that PC and the pyruvate shuttles are increased in ZF islets, and this accounts for glucose mitochondrial metabolism being increased when pyruvate dehydrogenase activity is reduced. As the anaplerosis pathways are implicated in glucose-induced insulin secretion and the synthesis of glucose-derived lipid and amino acids, our results highlight the potential importance of PC and the anaplerosis pathways in the enhanced insulin secretion and beta-cell growth that characterize beta-cell adaptation to insulin resistance.
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PMID:beta-Cell adaptation to insulin resistance. Increased pyruvate carboxylase and malate-pyruvate shuttle activity in islets of nondiabetic Zucker fatty rats. 1214 6

The effects of synthetic preparations exhibiting cytokinin-like activity (6-benzylaminopurine, Thidiazuron, and kartolin-2) on the specific leaf area (SLA) were studied in plants of the family Gramineae (wheat, Triticum aestivum L.; meadow fescue, Festuca pratensis Huds.; and reed fescue, F. arindinacea Schreb.). At the early stages of ontogeny (until the leaf area reached 50-60% of the maximum value), treatment of plants of the three species with cytokinin-like preparations caused an increase in SLA. The SLA value in these plants was correlated with the rate of photosynthetic assimilation of carbon dioxide and activities of carbon metabolism enzymes: ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39), NAD-malate dehydrogenase (EC 1.1.1.37), and NADP-glyceraldehydrophosphate dehydrogenase complex, which includes phosphoglycerate kinase (EC 2.7.2.3) and glyceraldehydrophosphate dehydrogenase (EC 1.2.1.13). However, there was no correlation of SLA with the activity of phospho(enol)pyruvate carboxylase (EC 4.1.1.31), an anaplerotic carboxylation enzyme of grasses. SLA is suggested to reflect the state and activity of the photosynthetic apparatus and can be recommended as a characteristic of photosynthesis variability (e.g., caused by cytokinin-like preparations).
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PMID:[Effect of preparations exhibiting cytokinin-like activity on the specific density of leaf in grasses]. 1244 1

We have studied source-sink relationships with a model consisting of single-rooted leaves without petioles. We previously reported that the rate of photosynthesis decreased when C4 model plants prepared from Amaranthus cruentus leaves were subjected to sink-limited conditions by exposure to continuous light for a few days. It was suggested that the inhibition is due to a coordinated decrease in the activity of ribulose-1,5-bisphosphate carboxylase (RuBPcase) and phosphoenol-pyruvate carboxylase (PEPcase), both essential enzymes for photosynthesis in C4 plants. We further investigated the mechanisms behind the decreased activity of RuBPcase, PEPcase, NAD-malic enzyme and NAD-malate dehydrogenase. The results suggested that (1) the initial activity of RuBPcase is suppressed by a lowering of the P(i) level in chloroplasts, (2) the inhibition of PEPcase is due to dephosphorylation of the enzyme via the inhibition of PEPcase kinase and PEPcase phosphatase, (3) the inhibition of NAD-malic enzyme and NAD-malate dehydrogenase is derived from the oxidation of these enzymes, and (4) some proteinous factor(s) may be involved in the inhibition of the activity of these latter three enzymes. The significance of a coordinated decrease in these enzymes in response to a change in the source-sink balance is discussed.
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PMID:Photosynthesis with single-rooted Amaranthus leaves. II. Regulation of ribuelose-1,5-bisphosphate carboxylase, phosphoenolpyruvate carboxylase, NAD-malic enzyme and NAD-malate dehydrogenase and coordination between PCR and C4 photosynthetic metabolism in response to changes in the source-sink balance. 1246 Nov 29


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